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Biomedical subjects

J Nedelman

Publications and source records attributed to J Nedelman.

10 recordsLinked to original sources

Quantitative PCR with internal controls.

We examine the use of internal controls for estimating the expected initial copy number of the target in a polymerase chain reaction (PCR). We base our investigation on an extended branching-process model. In terms of that model, we delineate the necessary assumptions for this methodology to yield approximately unbiased answers, and we provide means for testing some of those assumptions. We show how to design a series of PCRs to attain optimal precision of the estimate. We provide an algorithm for conducting the statistical analysis of the data, including a formula for a confidence interval for the unknown expected initial copy number.

Algorithms

Modelling length bias in a longitudinally-linked record system of HIV cases.

We compare numbers of hospital admissions for intravenous drug using (IVDU) HIV patients and other HIV patients in acute-care facilities in New York State. Data consist of routinely collected hospital-discharge reports from New York's Statewide Planning and Research Cooperative System, linked into longitudinal case histories. Because recognition of an IVDU depends on an opioid diagnosis on any record in the case history, the observed distribution of the number of admissions per case for recognized IVDU's is biased towards greater numbers of admissions. We develop and apply a model to overcome this biasing. Our findings reveal that the mean numbers of admissions for the two groups differ significantly, but less so than without recognition of the length biasing.

Bias

The prevalence of malaria in Garki, Nigeria: double sampling with a fallible expert.

Data from the Garki Project are analyzed to assess how misdiagnosis affects the estimated prevalence of Plasmodium falciparum. Three double-sampling models that account for the fallibility of the expert are derived and applied. The models incorporate information about the density of parasites in the blood to varying degrees. The error in the estimation of prevalence is quantified; and its dependence on calendar time, age, prevalence, and density is investigated. Prevalence and average density are discovered to be good predictors of the error, with the latter being better. Implications of the double-sampling models for the design of epidemiological surveys similar to the one in Garki are investigated.

Adolescent

Inference for an age-dependent, multitype branching-process model of mast cells.

We consider an age-dependent, multitype model for the growth of mast cells in culture. After a colony of cells is established by an initiator type, the two possible types of cells are resting and proliferative. Using novel inferential procedures, we estimate the generation-time distribution and the offspring distribution of proliferative cells, and the waiting-time distribution of resting cells.

Animals

A stochastic model for mast cell proliferation in culture.

A birth-death model was developed for the proliferation of mast cells. According to the model, each secondary mast cell colony starts with one proliferative cell. At each generation each cell chooses among three possibilities: 1) division into two proliferative cells; 2) division into two non-proliferative cells; or 3) disappearance. At each step, a non-proliferative cell either does nothing or disappears. A computer simulation of this model could be fitted reasonably well to our data for the size distributions of secondary mast cell colonies recorded after different culture periods. Our model predicts that proliferative cells comprise a larger fraction of the colony in large secondary colonies than in small ones. This prediction was successfully tested by examination of tertiary colony formation. This is a general model for cell proliferation that may be applicable to other types of cells.

Animals

Estimation for a model of multiple malaria infections.

The Macdonald-Dietz model for superinfection in malaria is a time-dependent infinite-server queue. However, the queue is only partially observable; it can be ascertained only as not empty or empty. Moreover, continuous observation of the queue is impossible. This paper derives likelihoods for the model's parameters with incomplete, multiwave panel data, and numerically maximizes those likelihoods for some data from a field study in Nigeria.

Biometry

Species specificity of Bordetella adherence to human and animal ciliated respiratory epithelial cells.

Bacteria of the genus Bordetella adhere preferentially to ciliated respiratory epithelial cells. We investigated the specificity of this unique tropism by assessing the concentration-dependent adherence of the three Bordetella species to ciliated cells from different hosts. Bordetella pertussis and Bordetella parapertussis adhere better to human ciliated cells than to those from rabbits, mice, or hamsters. In contrast, Bordetella bronchiseptica demonstrates preferential adherence to nonhuman mammalian ciliated cells of rabbits, mice, and hamsters. There was no attachment of any Bordetella organisms to chicken ciliated cells. These observations suggest that specificities of attachment may explain the marked predominance of B. pertussis as the cause of whooping cough in humans and of B. bronchiseptica as a respiratory pathogen of many nonhuman mammals.

Animals

A negative binomial model for sampling mosquitoes in a malaria survey.

Sampling models are investigated for counts of mosquitoes from a malaria field survey conducted by the World Health Organization in Nigeria. The data can be described by a negative binomial model for two-way classified counted data, where the cell means are constrained to satisfy row-by-column independence and the parameter k is constant across rows. An algorithm, based on iterative proportional fitting, is devised for finding maximum likelihood estimates. Sampling properties of the estimates and likelihood-ratio statistics for the small sample sizes of the data are investigated by Monte Carlo experiments. The WHO reported an observation that the relative efficiencies of four trapping methods vary over time. Out of eight villages in the survey area, this observation is found to be true in only the one village that is near a swamp.

Animals

Error analysis in flow microfluorometry.

Sources of error in a typical algorithm for the analysis of single flow-microfluorometric histograms are identified. A new statistical model for such data is presented, by means of which the error sources are quantitatively investigated. These theoretical investigations lead to three practical observations: A more detailed characterization of the fluorescence dispersion process is needed for a more refined algorithm. Levels of dispersion typically experienced are such that from a single histogram the distribution of cells within S-phase cannot be finely resolved; but the crude distribution of cells among the three phases G1, S, and G2-M may be accurately estimated. If currently typical levels of dispersion can be halved, then the S-phase distribution can be finely resolved.

DNA

Investigation into the experimental kinetic support of the two-state model of the cell cycle.

Five previously published cell generation-time distribution functions have been examined in an effort to elucidate the parameters of the two-state model of the cell cycle. These parameters are the fractional number of cells that bypass the G0 state, the probability of exit from G0, and the distribution of traversal times through the active state. To explain observed beta-curve behavior of cell populations, it is necessary to define the parameters in terms of pairwise behavior of newborn sister cells. From the beta-curve, we demonstrate that at least 50% of the cells must pass through the G0 state. The alpha-curve is consistent with any positive fraction of newborn cells passing through the G0 state, and provides no further information. We explore a possible method for resolving the remaining indeterminacy regarding the number of cells bypassing the G0 state, namely, examination of the generation-time distribution functions of fast sister cells only. Such an approach, although theoretically attractive, presents formidable experimental difficulties, however. If it should turn out that indeed only 50% of the cells are apparently passing through a random-exiting phase of the cell cycle, then an alterative plausible biological mechanism for the observed variability in generation times is supplied by Prescott's hypothesis: variability is a consequence of the inequality in the metabolic content of sister cells at birth.

Animals